The purpose of this project is to analyze the hormonal control of calcium metabolism during pregnancy, intra-uterine growth, postnatal development and lactation. In particular, these studies focus on the role of the vitamin D-endocrine system. An important role for vitamin D in developmental and reproductive biology is strongly supported by documented alterations in vitamin D metabolism and tissue responsives during pregnancy, lactation, and postnatal development. In addition, we have recently identified the vitamin D-dependent calcium binding protein (CaBP) in rat placenta and found coordinated changes in levels of placental and intestinal CaBP during pregnancy. Moreover, the intestinal levels of CaBP during lactation and neonatal development paralleled the calcium demands of the organism. Experiments are designed to assess the effects of in vivo changes in vitamin D metabolism upon placental CaBP and fetal mineralization and on maternal intestinal CaBP and calcium absorption. In these experiments, vitamin D metabolism will be altered by feeding high strontium, vitamin D deficient and low mineral diets to pregnant rats and by administration of active metabolites of vitamin D. Placental calcium binding protein (CaBP) will be characterized with respect to its vitamin D-dependency, messenger RNA (mRNA) production, induction in tissue culture, cellular localization and species distribution. The roles of prolactin and vitamin D metabolism in the intestinal adaptations during lactation will be assessed by the use of centrally-acting inhibitors and simulators of prolactin secretion. A fourth set of studies has the objective of elucidating the role of vitamin D metabolism in the postnatal development of intestinal calcium transport. This objective will be accomplished by: (a) determining the in vivo effects on intestinal development of vitamin D metabolites, thyroxine and adrenocorticoids, singly and in combination; (b) measurement of intestinal receptors for 1,25-(OH)2-cholecalciferol during postnatal development; and (c) the appearance of CaBP mRNA during development.